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Article: The role of the polyol pathway in acute kidney injury caused by hindlimb ischaemia in mice

TitleThe role of the polyol pathway in acute kidney injury caused by hindlimb ischaemia in mice
Authors
KeywordsAcute kidney injury
Aldose reductase inhibitor
Ischaemic hindlimb injury
Polyol pathway
Issue Date2010
PublisherJohn Wiley & Sons. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/1130
Citation
Journal Of Pathology, 2010, v. 220 n. 5, p. 530-541 How to Cite?
AbstractThe polyol pathway, a collateral glycolytic process, previously considered to be active in high glucose milieu, has recently been proposed to play a crucial role in ischaemia/reperfusion tissue injury. In this study, we explored the role of the polyol pathway in acute kidney injury (AKI), a life-threatening condition, caused by hindlimb ischaemia, and determined if inhibition of the polyol pathway by aldose reductase (AR) inhibitor is beneficial for this serious disorder. Mice 8 weeks of age rendered hindlimb ischaemic for 3 h by the clipping of major supporting arteries revealed marked muscle necrosis with accumulation of sorbitol and fructose in ischaemic muscles. Serum concentrations of blood urea nitrogen (BUN), creatinine phosphokinase (CPK), creatinine, tumour necrosis factor (TNF)-α as well as interleukin (IL)-6 were all elevated in these mice. Treatment with AR inhibitor (ARI) effectively suppressed muscle necrosis and accompanying inflammatory reactions and prevented renal failure. Similar to ARI-treated mice, AR-deficient mice were protected from severe ischaemic limb injury and renal failure, showing only modest muscle necrosis and significant suppression of serum markers of renal failure and inflammation. Thus, these findings suggest that the polyol pathway is implicated in AKI caused by ischaemic limb injury and that AR may be a potential therapeutic target for this condition. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Persistent Identifierhttp://hdl.handle.net/10722/124500
ISSN
2015 Impact Factor: 7.381
2015 SCImago Journal Rankings: 4.176
ISI Accession Number ID
Funding AgencyGrant Number
Ministry of Education, Science, Culture, and Sports, Japan14370073
18659106
Funding Information:

This study was supported by a grant-in-aid from the Ministry of Education, Science, Culture, and Sports, Japan (Nos 14370073 and 18659106) to S Yagihashi.

References

 

DC FieldValueLanguage
dc.contributor.authorYagihashi, Sen_HK
dc.contributor.authorMizukami, Hen_HK
dc.contributor.authorOgasawara, Sen_HK
dc.contributor.authorYamagishi, SIen_HK
dc.contributor.authorNukada, Hen_HK
dc.contributor.authorKato, Nen_HK
dc.contributor.authorHibi, Cen_HK
dc.contributor.authorChung, Sen_HK
dc.contributor.authorChung, Sen_HK
dc.date.accessioned2010-10-31T10:37:53Z-
dc.date.available2010-10-31T10:37:53Z-
dc.date.issued2010en_HK
dc.identifier.citationJournal Of Pathology, 2010, v. 220 n. 5, p. 530-541en_HK
dc.identifier.issn0022-3417en_HK
dc.identifier.urihttp://hdl.handle.net/10722/124500-
dc.description.abstractThe polyol pathway, a collateral glycolytic process, previously considered to be active in high glucose milieu, has recently been proposed to play a crucial role in ischaemia/reperfusion tissue injury. In this study, we explored the role of the polyol pathway in acute kidney injury (AKI), a life-threatening condition, caused by hindlimb ischaemia, and determined if inhibition of the polyol pathway by aldose reductase (AR) inhibitor is beneficial for this serious disorder. Mice 8 weeks of age rendered hindlimb ischaemic for 3 h by the clipping of major supporting arteries revealed marked muscle necrosis with accumulation of sorbitol and fructose in ischaemic muscles. Serum concentrations of blood urea nitrogen (BUN), creatinine phosphokinase (CPK), creatinine, tumour necrosis factor (TNF)-α as well as interleukin (IL)-6 were all elevated in these mice. Treatment with AR inhibitor (ARI) effectively suppressed muscle necrosis and accompanying inflammatory reactions and prevented renal failure. Similar to ARI-treated mice, AR-deficient mice were protected from severe ischaemic limb injury and renal failure, showing only modest muscle necrosis and significant suppression of serum markers of renal failure and inflammation. Thus, these findings suggest that the polyol pathway is implicated in AKI caused by ischaemic limb injury and that AR may be a potential therapeutic target for this condition. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.en_HK
dc.languageengen_HK
dc.publisherJohn Wiley & Sons. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/1130en_HK
dc.relation.ispartofJournal of Pathologyen_HK
dc.rightsJournal of Pathology. Copyright © John Wiley & Sons.-
dc.subjectAcute kidney injuryen_HK
dc.subjectAldose reductase inhibitoren_HK
dc.subjectIschaemic hindlimb injuryen_HK
dc.subjectPolyol pathwayen_HK
dc.subject.meshAcute Kidney Injury - etiology - metabolism - pathology - prevention and control-
dc.subject.meshHindlimb - blood supply-
dc.subject.meshIschemia - complications - metabolism - pathology-
dc.subject.meshMuscle, Skeletal - metabolism - pathology-
dc.subject.meshPolymers - metabolism-
dc.titleThe role of the polyol pathway in acute kidney injury caused by hindlimb ischaemia in miceen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-3417&volume=220&issue=5&spage=530&epage=541&date=2010&atitle=The+role+of+the+polyol+pathway+in+acute+kidney+injury+caused+by+hindlimb+ischaemia+in+miceen_HK
dc.identifier.emailChung, S: skchung@hkucc.hku.hken_HK
dc.identifier.emailChung, S: smchung@hkucc.hku.hken_HK
dc.identifier.authorityChung, S=rp00381en_HK
dc.identifier.authorityChung, S=rp00376en_HK
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1002/path.2671en_HK
dc.identifier.pmid20112370-
dc.identifier.scopuseid_2-s2.0-77949853353en_HK
dc.identifier.hkuros181845en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77949853353&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume220en_HK
dc.identifier.issue5en_HK
dc.identifier.spage530en_HK
dc.identifier.epage541en_HK
dc.identifier.isiWOS:000275969300003-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridYagihashi, S=7006805482en_HK
dc.identifier.scopusauthoridMizukami, H=35412986100en_HK
dc.identifier.scopusauthoridOgasawara, S=23095589000en_HK
dc.identifier.scopusauthoridYamagishi, SI=7102183565en_HK
dc.identifier.scopusauthoridNukada, H=7003749268en_HK
dc.identifier.scopusauthoridKato, N=26643144400en_HK
dc.identifier.scopusauthoridHibi, C=6506064348en_HK
dc.identifier.scopusauthoridChung, S=7404292976en_HK
dc.identifier.scopusauthoridChung, S=14120761600en_HK

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